From January to July 1991, an outbreak of mumps occurred in Maury County, Tennessee. At the primarily affected high school, where 98% of students and all but 1 student with mumps had been vaccinated before the outbreak, 68 mumps cases occurred among 1116 students (attack rate, 6.1%). Students vaccinated before 1988 (the first year mumps vaccination was required for school attendance in Tennessee) may have been at greater risk of mumps than those vaccinated later (65[6.1%] of 1001 vs. 2[2.2%] of 89; risk ratio, 2.9; 95% confidence interval, 0.7-11.6). Of 13 persons with confirmed mumps who underwent serologic testing, 3 lacked IgM antibody in well-timed acute- and convalescent-phase serum specimens. Vaccine failure accounted for a sustained mumps outbreak in a highly vaccinated population. Most mumps cases were attributable to primary vaccine failure. It is possible that waning vaccine-induced immunity also played a role.